Zhu Min, Wang Hongyi, Cui Jiantao, Li Wenmei, An Guo, Pan Yuanming, Zhang Qingying, Xing Rui, Lu Youyong
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Laboratory of Molecular Oncology, Peking University Cancer Hospital and Institute, Beijing 100142, China.
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Surgery, Peking University Cancer Hospital and Institute, Beijing 100142, China.
Cell Death Dis. 2017 Jul 20;8(7):e2938. doi: 10.1038/cddis.2017.297.
S100A14 is a calcium-binding protein involved in cell proliferation and differentiation as well as the metastasis of human tumors. In this study, we characterized the regulation of S100A14 expression between biological signatures and clinical pathological features in gastric cancer (GC). Our data demonstrated that S100A14 induced the differentiation of GC by upregulating the expression of E-cadherin and PGII. Moreover, S100A14 expression negatively correlated with cell migration and invasion in in vitro and in vivo experimental models. Interestingly, S100A14 blocked the store-operated Ca influx by suppressing Orai1 and STIM1 expression, leading to FAK expression activation, focal adhesion assembly and MMP downregulation. Taken together, our results indicate that S100A14 may have a role in the induction of differentiation and inhibition of cell metastasis in GC.
S100A14是一种钙结合蛋白，参与细胞增殖、分化以及人类肿瘤的转移。在本研究中，我们对胃癌（GC）生物学特征与临床病理特征之间S100A14表达的调控进行了表征。我们的数据表明，S100A14通过上调E-钙黏蛋白和PGII的表达来诱导GC分化。此外，在体外和体内实验模型中，S100A14表达与细胞迁移和侵袭呈负相关。有趣的是，S100A14通过抑制Orai1和STIM1的表达来阻断储存式钙内流，导致FAK表达激活、粘着斑组装和MMP下调。综上所述，我们的结果表明S100A14可能在GC的分化诱导和细胞转移抑制中发挥作用。
